Development of Innovative Medicines in Russian Academic Institutes.

The Experience of Nonprofit Partnership “Orchemed”

Prof. Sergey Bachurin, corresponding-member of Russian Academy of Sciences

Examples of innovative drug-candidates developed in the institutes

of Russian Academy of Sciences

Chemical synthesis of conjugated vaccine against Staphylococcus aureus

Conjugated vaccine

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Introducing of spacer groups,glycosylation reactions,

Removal of blocking groups.

Protein-carrier (dTT)

Protective efficacy against the infection of mice with methicillin-resistant Staphylococcus aureus (MRSA) strain

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Collaboration: Zelinsky Institute, RAS (chemical synthesis) and Harvard Medical School (bacteriology) Marina Gening, T. Maira, A. Kropec, D. Skurnik, Y. Tsvetkov, N. Nifantiev*, G. Pier* «Synthetic β(16)-linked N-acetylated and non- acetylated oligoglucosamines to produce conjugate vaccines for bacterial pathogens» Infect. Immun., 78 (2009) 764-772.

Zelinsky Institute RAS Harvard Medical School

Institute of Physiologically Active Compounds RAS and Institute of Normal Physiology RAMS

Development of new generation of memory-enhancers and neuroprotectors

3D-docking of binary AMPA-receptor modulators

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Restoration of weak or lost memory in animal models

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Novel neuroprotective agents developed, which block proteinopathy in different animal models of neurodegeneration (TDP-43 protein and gamma-synuclein transgenic animals)

Wild-type Symptomatic TG TG + IP-0012

Contractual work with Bayer AG, Pfizer, AC Immune (Switzerland)

Development of novel generation of drugs on the basis of natural and synthetic nanosupports

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Clathrates of pharmacones with nano-matrixes of plant origin – the new approach for increasing efficacy, bioavalability and decreasing toxicity of known drugs

«Symvaglysin» clathrate of simvastatin with glycyrrhyzic acid (GA)– new cholesterol-lowering agent (with ED reduced in 3 times).Clathrate of GA with allapenine – new safe anti-arrythmic more active and less toxic than medicine Allapenine, IOC Ufa (The above agents are approved for clinical trials)

Institute of Organic Chemistry, RAS, Ufa

Novosibirsk Institute of Organic Chemistry RAS

Institute of Problem of Institute of Physiologically Chemical Physics, RAS, Active Compounds, RAS

Original complexes of C60-fullerene and soluble polymers with known medicines (developed in IPCP and IPAC RAS) showed significantly improved pharmacological profile of these medicines.

(both from Chernogolovka, Moscow region)

Institute of Organic Synthesis (IOS, Ekaterinburg, Ural Branch RAS)

ANTI-VIRAL AGENT «TRIAZAVERIN»: laboratory to the marketlaboratory to the market

Broad spectrum of anti-virus activity (human and chicken influenza, PC-infection, vernal

encephalitis, etc). Clinical trials are under completion.

Produced and certified more than

20 000 capsule

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Highly efficient antibacterials in series of fluoroquinolones with broad spectrum of biological activity. Technology of its production is developed

PEFLOXACIN

LISOMUSTIN a new anti-cancer

agent

Development and manufacture of highly-requested medicines for Russian pharma market

To consolidate the researches of academic institutes in the field of drug discovery the Nonprofit Partnership “OrCheMed” (Organic-Chemistry for

Medicine) of more than 10 leading academic institutes was founded in 2005. It unites scientific and innovative potential

of about 3000 scientists.

Ins.Probl.Chem. Phys. RAS(Chernogolovka)

Ins.Org.Phys. Chem. RAS

(Kazan)

INEOS RAS (Moscow)

IPAC RAS(Chernogolovka)

Ins.Org.Chem. RAS (UFA)

IOC RAS(Москва)

Ins.Org. Synth. Ural Branch RAS

(Ekaterinburg)

IBOC RAS(Moscow)

Novosibirsk Inst. Org.Chem.RAS

Ins.Chem. RAS (Rep. Komi)

1200 including > 600 scientific personnel

730 including 470 scientific personnel

200 including 110 scientific personnel

700 including 300 scientific personnel

200 including 130 scientific personnel

450 including 250 scientific personnel

200 including 130 scientific personnel

800 including 380 scientific personnel

180 including 130 scientific personnel

450 including 250 scientific personnel

•Analyzing of chemical compounds libraries, developed in different institutes.•Organizing of virtual and biological screening of chemical compounds libraries. •Providing the pharmacological and marketing expertise for hit-compounds developed in the institutes.•Foundation of novel start-up companies;•Development of nascent IP from consortium members through project funding and licensing.

MISSION:

Modern centers for preclinical trials in the Russian Academy of Sciences.

Laboratory for Bioscreening (Puschino Branch of the Institute of Bioorganic

Chemistry)

Center for preclinical trials in Chernogolovka

Siberian Center for animal genetic

models

(Novosibirsk)

• In vivo screening of active compounds• Toxicological and safety study of lead-

compounds. • The full-cycle of preclinical trials

“Traditional” Drug Discovery Strategy

Synthesis of new

compounds

Screening (computational

and bio-screening) Pre-Clinical

Trials (GLP)

Hit-Compounds optimization

appr. 1 000 000 comp. (1000 comp.)

Lead-Compounds optimization

(100 comp.)Drug-candidates

(10)

1 PHASE (60-70% success)

CLINICAL TRIALS

«Nature Rev.Drug Disc.» 2004-2007Drug discovery (R&D)

2 PHASE (25-40% success)

3 PHASE (40-60% success)

1 DRUG ON THE MARKET

Appr. 15 years

About US$ 1BL

“Orchemed” should cover the “Nishe” of accumulation of chemical libraries datebases and selection and commercialization of hit- and lead-compounds

Synthesis of new

compounds

Screening (computational

and bio-screening) Pre-Clinical

Trials (GLP)

Hit-Compounds optimization

appr. 1 000 000 comp. (1000 comp.)

Lead-Compounds optimization

(100 comp.)Drug-candidates

(10)

1 PHASE (60-70% success)

CLINICAL TRIALS

NP “OrCheMed”

2 PHASE (25-40% success)

3 PHASE (40-60% success)

Medicinal chemistry approaches decrease time and cost of R&D stages

“Orchemed” as a “catalyst” of drug discovery process in academician institutes

Centers for preclinical trials

Portfolio:

>50 projects in actual pharmacological areas

Project portfolio

Antiviral drug BG-122 (INEOS RAS) Anticoagulant LS-27 (IOS UrB RAS) Antineurodegenerative drug RU-32 (IPAC RAS) Antiinflammatory drugs (Yaroslavl SU) Antiparkinson drugs (IOC Novosibirsk) Cardiovascular drug Dibornol (IC Syktyvkar) Antitumor drugs (IOS, IPCP) Advanced drug delivery systems (IPAC, INEOS, IPCP) etc.

www.orchemed.com +7 (496) 524-2563

Recognized academic expert group

• Invited experts for State Duma, government, mass media, etc. • Official codevelopers of Strategy of Development of Pharmaceutical Industry of Russian Federation in 2008-2020 (Pharma-2020) • Expert evaluation of work projects for business groups• Initiator of strategic national projects, such as National bioscreening network• Strategic partnership with Russian innovative (bio)pharmaceutical companies, biopharmclusters, etc.

Presentation of Orchemed initiative Project ”National

Bioscreening Network” in State Duma

Presentation of Orchemed Projects to Minister E.Nabiulina and ROSNANO Head A.Chubajs

Participation in State Duma Committee Workshop

www.orchemed.com +7 (496) 524-2563

Model of commercialization

Institutes of RAS

Business partners• Binnopharm

One of the biggest GMP manufacturers in Russia

• Biopharmacluster BioCity

• Maxwell Biotech

• International fund of technology and Investment

• Obninsk pharmcluster “Park of active molecules”

• and many other scientific and business organizations in Russia and former USSR

NP OrchemedIP rights

Royalties from license agreements

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es

Venture funds (e.g., Russian

venture company)

or

Pharmaceutical companies

capital investments

Startup-1Startup-2

Startup-3Startup-4

Startup-5

out-licensing

Typical distribution of shares in start-up:

Scientists-developers – 75%

NP Orchemed – 25%www.orchemed.com

+7 (496) 524-2563

National Bioscreening Centers Network, NBCN (Project, developed jointly by RAS, RAMS, MSU and NP Orchemed)The main goals of the project (2010-2012): 1. Development and launch an integrated infrastructure of biological screening in

Russia for providing discovery of novel innovative medicines.2. Development of series (30-50) of highly efficient lead-compounds for the most

requested fields of medicine and launch of 3-4 innovative drugs on Russian pharma market at 2020.

Proposed Structure of NBCN

Thank you for your attention!

- In 2007, the global pharmaceutical market grew to US$712 billion (what is about 80% of Global Oil Market). - Year-on-year the global pharmaceutical market increased to 10.7% in 2007, largely as a result of strong sales for new innovative products and high market growth in emerging pharmaceutical markets such as China, India and Russia. - It is expected that the global pharmaceutical market is forecast to grow to US$929 billion in 2012. The report “Pharmaceutical Market Trends, 2008 - 2012”

According to the “Strategy of the development of Russian pharmaceutical industry till 2020”, approved by the Russian Government it is expected that about 30% of all drugs in Russian Pharma Market will be new innovative medicines. Therefore one of the main line of activity of Russian Academy of Science is the provision of fundamental scientific background for the development of novel promising drug-candidates.

The most fundamental and lasting subject of synthesis is not production of new compounds,

but production of properties.

George S. Hammond. Norris Award Lecture, 1968

Drug Discovery – One of the Most Requested Field of Chemistry

Nonprofit partnership of chemical institutes of RAS

«Orchemed» (Organic Chemistry for Medicine).

General informationEstablished in 2005

The legal status: nonprofit partnership

Founders: Institutes of RAS

Management:Scientific Board (Chairman – Acad. N.S. Zefirov), Board of experts (Chairman – Corr. Member of RAS S.O. Bachurin), Director (K.V. Balakin, PhD, DSc)

Institutes-members: 11 institutes of RAS: Institute of Physiologically Active Compounds, Institute of Problem of Chemical Physics, Institute of Organic Chemistry, Institute of Elementorganic Compounds, Institute of Bioorganic Chemistry (all from Moscow area), Institute of Organic and Physical Chemistry (Kazan), Institute of Chemistry (Syktyvkar), Institute of Organic Chemistry (Ufa), Institute of Organic Synthesis (Ekaterinburg), Institute of Organic Chemistry (Novosibirsk), Institute of Chemistry of Solutions (Ivanovo)

www.orchemed.com +7 (496) 524-2563

Features

Orchemed – Russian biggestcooperative academic initiative in the field of drug discovery and development

Complete cycle of preclinical innovative drug discoveryFrom virtual screening to preclinical animal studies

Portfolio of innovative projectsMore than 50 projects in actual therapeutic areas

Focus on innovative developments Distinctive feature of academic projects

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Pirenzepine(Boehringer Ingelheim)

Zolenzepine(Byk Gulden)

Telenzepine(Byk Gulden)

Orchemed’s Mission: To identify and promote prospective technologies developed in Russian

academic institutes, and pave the way to effective technology transfer to national and global

pharmaceutical industrywww.orchemed.com

+7 (496) 524-2563

Drug Discovery: as a rate-limiting step in Drug Development

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NFocused chemical Focused chemical

librarieslibraries

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Drug-candidatesDrug-candidates

Chemical Chemical compounds compounds

librarieslibraries

HTP-screening systems

Virtual prescreening

Optimization of hit- and lead- compounds

In vivo testing and preclinical trials

of lead-compounds

Video camera

Water pool Hidden Platform

Animal (rat)

“Weak Link” !

National Bioscreening Centers Network, NBCN (Project, developed by NP Orchemed jointly with RAS)

The main goals of the project (2010-2012): Development and launching an integrated infrastructure of biological

screening in Russia for providing discovery of novel innovative medicinesDevelopment of series (30-50) of highly efficient lead-compounds for the

most requested fields of medicine as a potential innovative drugs on Russian market at 2020.

Ufa